Lapatinib Ditosylate and Capecitabine in Treating Patients With Stage IV Breast Cancer and Brain Metastases

Launched by UNICANCER · Aug 26, 2009

Keywords

ClinConnect Summary

OBJECTIVES:

Primary

* To assess the objective response rate by volumetric analysis of brain metastasis as assessed by MRI in patients with HER2-positive stage IV breast cancer treated with lapatinib ditosylate and capecitabine.

Secondary

* To document any toxicity evaluated by NCI CTC v3.0.
* To assess the time to radiotherapy.
* To document the time to disease progression in the central nervous system (CNS) of these patients.
* To evaluate the overall response rate for extra-CNS disease.
* To assess the clinical benefit (complete response, partial response, and stable disease for ≥ 6 m...

Gender

ALL

Eligibility criteria

• DISEASE CHARACTERISTICS:
• • Histologically confirmed invasive breast cancer
• • Stage IV disease
• • At least 1 measurable CNS lesion ≥ 10 mm on T1-weighted gadolinium-enhanced MRI
• • No single brain metastasis that could be treated by surgery
• • HER-2 positive primary tumor as defined as IHC3+ or IHC2+ and FISH-positive
• • Hormone receptor status: not specified
• PATIENT CHARACTERISTICS:
• • Menopausal status not specified
• • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• • Life expectancy ≥ 3 months
• • Absolute Neutrophil Count (ANC) ≥ 1,000/mm\^3
• • Platelet count ≥ 100,000/mm\^3
• • Hemoglobin ≥ 10g/dL
• • Creatinine ≥ 1.5 times upper limit of normal (ULN)
• • Albumin ≥ 2.5 g/dL
• • Serum bilirubin ≤ 1.5 times ULN (unless due to Gilbert's syndrome)
• • ASAT and ALAT ≤ 3 times ULN (≤ 5 times ULN with documented liver metastasis)
• • Not pregnant or nursing
• • Negative pregnancy test
• • Fertile patients must use effective contraception 2 weeks before, during, and for 28 days after completion of study treatment (female) or for 1 week after completion of treatment (male)
• • Able to swallow and retain oral medication
• • Affiliated to a Social Security System
• • No known contraindication to MRI
• • No prior or active malignancy, unless disease free for ≥ 10 years
• * No other concurrent severe and/or uncontrolled medical disease which could compromise study participation, including any of the following:
• • Infection
• • Cardiac disease (e.g., uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within the past year, Left Ventricular EJection Fraction (LVEF) \> grade 2)
• • Current active hepatic or biliary disease (except for Gilbert syndrome, asymptomatic gallstones, liver metastasis or stable chronic liver disease per investigator assessment)
• • Renal disease
• • Active gastrointestinal (GI) tract ulceration, malabsorption syndrome, active uncontrolled ulcerative colitis, or disease significantly affecting GI function
• • Severely impaired lung function (e.g., spirometry and diffusion capacity of lung for carbon monoxide (DLCO) ≤ 50% of normal, and O_2 saturation ≤ 88% at rest on room air)
• • No known dihydropyrimidine dehydrogenase deficiency
• • No significantly altered mental status prohibiting the understanding of the study, or with psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• • Not deprived of liberty or placed under the authority of a tutor
• PRIOR CONCURRENT THERAPY:
• • At least 2 weeks since prior breast cancer treatment (e.g., trastuzumab, chemotherapy, immunotherapy or biological response modifiers, endocrine therapy, or radiotherapy)
• • More than 30 days since prior investigational drugs
• • More than 14 days since prior and no concurrent strong inhibitors or inducers of the cytochrome P450 isoenzyme 3A4 (CYP3A4) (i.e., clarithromycin, ketoconazole, itraconazole, voriconazole, ritonavir)
• • No prior whole brain radiotherapy (WBRT) or brain stereotactic radiotherapy
• • No prior treatment with capecitabine and/or lapatinib ditosylate
• • No prior resection of the stomach or small bowel
• • No concurrent systemic treatment or radiation therapy for breast cancer (except corticosteroid, bisphosphonates, or mannitol)